The assessment of imaging biomarkers is critical for advancing precision medicine and improving disease characterization. Despite the availability of methods to derive disease heterogeneity metrics in imaging studies, a robust framework for evaluating measurement uncertainty remains underdeveloped. To address this gap, we propose a novel Bayesian framework to assess the precision of disease heterogeneity measures in biomarker studies. Our approach extends traditional methods for evaluating biomarker precision by providing greater flexibility in statistical assumptions and enabling the analysis of biomarkers beyond univariate or multivariate normally-distributed variables. Using Hamiltonian Monte Carlo sampling, the framework supports both, for example, normally-distributed and Dirichlet-Multinomial distributed variables, enabling the derivation of posterior distributions for biomarker parameters under diverse model assumptions. Designed to be broadly applicable across various imaging modalities and biomarker types, the framework builds a foundation for generalizing reproducible and objective biomarker evaluation. To demonstrate utility, we apply the framework to whole-body diffusion-weighted MRI (WBDWI) to assess heterogeneous therapeutic responses in metastatic bone disease. Specifically, we analyze data from two patient studies investigating treatments for metastatic castrate-resistant prostate cancer (mCRPC). Our results reveal an approximately 70 tumors across both studies, objectively characterizing differential responses to systemic therapies and validating the clinical relevance of the proposed methodology. This Bayesian framework provides a powerful tool for advancing biomarker research across diverse imaging-based studies while offering valuable insights into specific clinical applications, such as mCRPC treatment response.

This study aimed to assess the accuracy of fat fraction estimation with clinically available Dixon sequences in normal-appearing marrow and bone metastases in the pelvis of metastatic prostate cancer patients. A prospective single-centre study was conducted with metastatic prostate cancer patients and healthy volunteers. Linearity and bias of fat fraction estimates from clinically available Dixon sequences were assessed against a 6-point PDw gradient echo (q-Dixon) sequence measuring the reference standard proton density fat fraction. Lesion fat fraction estimates were cross-compared using the Friedman test. Repeatability in volunteers was evaluated with Bland-Altman plots. Sensitivity of fat fraction estimates using TSE-Dixon sequences to specific absorption rate (SAR) related modifications were evaluated with correlation plots. Thirty-three patients were recruited for this study. Significant (p < 0.05) absolute bias (12.4

AI-based MRI reconstruction techniques improve efficiency by reducing acquisition times whilst maintaining or improving image quality. Recent recommendations from professional bodies suggest centres should perform quality assessments on AI tools. However, monitoring long-term performance presents challenges, due to model drift or system updates. Radiologist-based assessments are resource-intensive and may be subjective, highlighting the need for efficient quality control (QC) measures. This study explores using image quality metrics (IQMs) to assess AI-based reconstructions. 58 patients undergoing standard-of-care rectal MRI were imaged using AI-based and conventional T2-weighted sequences. Paired and unpaired IQMs were calculated. Sensitivity of IQMs to detect retrospective perturbations in AI-based reconstructions was assessed using control charts, and statistical comparisons between the four MR systems in the evaluation were performed. Two radiologists evaluated the image quality of the perturbed images, giving an indication of their clinical relevance. Paired IQMs demonstrated sensitivity to changes in AI-reconstruction settings, identifying deviations outside ± 2 standard deviations of the reference dataset. Unpaired metrics showed less sensitivity. Paired IQMs showed no difference in performance between 1.5 T and 3 T systems (p > 0.99), whilst minor but significant (p < 0.0379) differences were noted for unpaired IQMs. IQMs are effective for QC of AI-based MR reconstructions, offering resource-efficient alternatives to repeated radiologist evaluations. Future work should expand this to other imaging applications and assess additional measures.

A short quality control acquisition was developed to detect hardware issues and receiver coil positioning errors in whole-body MRI (WB-MRI). Individual coil element images were reconstructed to investigate potential broken elements and coil positioning was assessed by comparison with images acquired using the integral body coil. This approach was implemented in a group of healthy volunteers and patients with myeloma and successfully identified a previously undetected broken coil element. The expected signal difference between coil array and integral body coil images was defined and deviation from this expected profile was used to distinguish images acquired with deliberately imperfect coil set-ups.

Background Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test–retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT). Materials and Methods Thirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test–retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability. Results For the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC > 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (>0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively). Conclusions The ADC-based radiomic analysis shows better test–retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change.

Purpose To evaluate robustness and repeatability of magnetic resonance imaging (MRI) texture features in water and tissue phantom test-retest study. Materials and methods Separate water and tissue phantoms were imaged twice with the same protocol in a test-retest experiment using a 1.5-T scanner. Protocols were acquired to favour signal-to-noise ratio and resolution. Forty-six features including first order statistics and second-order texture features were extracted, and repeatability was assessed by calculating the concordance correlation coefficient. Separately, base image noise and resolution were manipulated in an in silico experiment, and robustness of features was calculated by assessing percentage coefficient of variation and linear correlation of features with noise and resolution. These simulation data were compared with the acquired data. Features were classified by their degree (high, intermediate, or low) of robustness and repeatability. Results Eighty percent of the MRI features were repeatable (concordance correlation coefficient > 0.9) in the phantom test-retest experiment. The majority (approximately 90%) demonstrated a strong or intermediate correlation with image acquisition parameter, and 19/46 (41%) and 13/46 (28%) of features were highly robust to noise and resolution, respectively (coefficient of variation < 5%). Agreement between the acquired and simulation data varied, with the range of agreement within feature classes between 11 and 92%. Conclusion Most MRI features were repeatable in a phantom test-retest study. This phantom data may serve as a lower limit of feature MRI repeatability. Robustness of features varies with acquisition parameter, and appropriate features can be selected for clinical validation studies.

Purpose: To characterize the voxel-wise uncertainties of Apparent Diffusion Coefficient (ADC) estimation from whole-body diffusion-weighted imaging (WBDWI). This enables the calculation of a new parametric map based on estimates of ADC and ADC uncertainty to improve WBDWI imaging standardization and interpretation: NoIse-Corrected Exponentially-weighted diffusion-weighted MRI (niceDWI). Methods: Three approaches to the joint modeling of voxel-wise ADC and ADC uncertainty (σADC) are evaluated: (i) direct weighted least squares (DWLS), (ii) iterative linear-weighted least-squares (IWLS), and (iii) smoothed IWLS (SIWLS). The statistical properties of these approaches in terms of ADC/σADC accuracy and precision is compared using Monte Carlo simulations. Our proposed post-processing methodology (niceDWI) is evaluated using an ice-water phantom, by comparing the contrast-to-noise ratio (CNR) with conventional exponentially-weighted DWI. We present the clinical feasibility of niceDWI in a pilot cohort of 16 patients with metastatic prostate cancer. Results: The statistical properties of ADC and σADC conformed closely to the theoretical predictions for DWLS, IWLS, and SIWLS fitting routines (a minor bias in parameter estimation is observed with DWLS). Ice-water phantom experiments demonstrated that a range of CNR could be generated using the niceDWI approach, and could improve CNR compared to conventional methods. We successfully implemented the niceDWI technique in our patient cohort, which visually improved the in-plane bias field compared with conventional WBDWI. Conclusions: Measurement of the statistical uncertainty in ADC estimation provides a practical way to standardize WBDWI across different scanners, by providing quantitative image signals that improve its reliability. Our proposed method can overcome inter-scanner and intra-scanner WBDWI signal variations that can confound image interpretation.

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Background Interpretation of diffusion in conjunction with T-2-weighted MRI is essential for assessing prostate cancer; however, the combination of apparent diffusion coefficient (ADC) with quantitative T-2 mapping remains unexplored. Purpose To document the T-2 components and ADC of untreated and irradiated nonmalignant prostate tissue as a measure of their glandular luminal and cellular compartments and to compare values with those of tumor. Study Type Prospective. Population Twenty-four men with prostate cancer (14 untreated; 10 with biochemical recurrence following radiation therapy). Field Strength/Sequences Endorectal 3 T MRI including a 32-echo gradient echo and spin echo (GRASE) and an 8 b-value diffusion-weighted sequence. Assessment Regions of interest were drawn on ADC maps and T-2-weighted images around focal lesions in areas of biopsy-positive prostate cancer and in nonmalignant areas of untreated and irradiated peripheral zone (PZ), and untreated transitional zone (TZ). Multiecho T-2 data were fitted with mono-/biexponential decay and nonnegative least squares functions. The luminal water fraction (LWF) was derived. Statistical Tests The preference between mono- and biexponential decay was assessed using the Bayesian information criterion. Differences in fitted parameters between tissue types were compared (paired t-test within groups, Kruskal-Wallis and Wilcoxon rank-sum test between groups) and correlations between ADC and T-2 components assessed (Spearman rank correlation test). Results LWF in tumor (0.09) was significantly lower than in PZ or TZ (0.27 and 0.18, P < 0.01, respectively), but tumor values were comparable to nonmalignant irradiated prostate (0.08). The short T-2 relaxation rate was lower in tumor than in nonmalignant untreated or irradiated tissue (significant compared with TZ, P = 0.01). There was a strong correlation between LWF and ADC in normal untreated tissue (r = 0.88, P < 0.001). This relationship was absent in nonmalignant irradiated prostrate (r = -0.35, P = 0.42) and in tumor (r = -0.04, P = 0.88). Data Conclusion T-2 components in conjunction with ADC can be used to characterize untreated and irradiated nonmalignant prostate and tumor. LWF is most useful at discriminating tumor in the untreated prostate. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:619-627.

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCTD). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p   =  0.05). Compared to sCTD and sCTDS, planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems.

During production an error was introduced in the article. 'The PCA-denoising MATLAB script can be found in Supplemental Digital Content 1 (stacks.iop.org/ PMB/64/105015/mmedia)'. should appear as 'The PCA-denoising MATLAB script can be found as Supplemental Digital Content 1 (stacks.iop.org/ PMB/64/105015/mmedia) to this article and is available at github (https://github.com/oliverchampion/PCA denoising.git)'.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10-5mm2s-1) was repeatable (upper and lower 95% limits of agreement of 12 × 10-5mm2s-1 [95% confidence interval {CI}: 6 × 10-5mm2s-1 to 18 × 10-5mm2s-1] and -15 × 10-5mm2s-1 [95% CI: -21 × 10-5mm2s-1 to -9 × 10-5mm2s-1]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Materials and Methods: Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.4 Gy in 28 daily fractions, over 5.5 weeks). The following parameter estimates were assessed in the whole tumor volume at baseline and following radiotherapy: apparent diffusion coefficient (ADC), parameters of the intra-voxel incoherent motion model of diffusion-weighted MRI (D, f, D*), transverse relaxation rate, fat fraction, and enhancing fraction after gadolinium-based contrast injection. Correlation was evaluated between pre-operative quantitative parameters and histopathological assessments of cellularity and fat fraction in post-surgical specimens (ClinicalTrials.gov , registration number NCT01902667). Results: Upper and lower 95% limits of agreement were 7.1 and -6.6%, respectively for median ADC at baseline. Median ADC increased significantly post-radiotherapy. Pre-operative ADC and D were negatively correlated with cellularity (r = -0.42, p = 0.01, 95% confidence interval (CI) -0.22 to -0.59 for ADC; r = -0.45, p = 0.005, 95% CI -0.25 to -0.62 for D), and fat fraction from Dixon MRI showed strong correlation with histopathological assessment of fat fraction (r = 0.79, p = 10(-7), 95% CI 0.69-0.86). Conclusion: Fat fraction on MRI corresponded to fat content on histology and therefore contributes to lesion characterization. Measurement repeatability was excellent for ADC; this parameter increased significantly post-radiotherapy even in disease categorized as stable by size criteria, and corresponded to cellularity on histology. ADC can be utilized for characterizing and assessing response in heterogeneous retroperitoneal sarcomas.

Despite the utility of tumour characterisation using quantitative parameter maps from multi- b -value diffusion-weighted MRI (DWI), clinicians often prefer the use of the image with highest diffusion-weighting ( b -value), for instance for defining regions of interest (ROIs). However, these images are typically degraded by noise, as they do not utilize the information from the full acquisition. We present a principal component analysis (PCA) approach for model-free denoising of DWI data. PCA-denoising was compared to synthetic MRI, where a diffusion model is fitted for each voxel and a denoised image at a given b -value is generated from the model fit. A quantitative comparison of systematic and random errors was performed on data simulated using several diffusion models (mono-exponential, bi-exponential, stretched-exponential and kurtosis). A qualitative visual comparison was also performed for in vivo images in six healthy volunteers and three pancreatic cancer patients. In simulations, the reduction in random errors from PCA-denoising was substantial (up to 55%) and similar to synthetic MRI (up to 53%). Model-based synthetic MRI denoising resulted in substantial (up to 29% of signal) systematic errors, whereas PCA-denoising was able to denoise without introducing systematic errors (less than 2%). In vivo , the signal-to-noise ratio (SNR) and sharpness of PCA-denoised images were superior to synthetic MRI, resulting in clearer tumour boundaries. In the presence of motion, PCA-denoising did not cause image blurring, unlike image averaging or synthetic MRI. Multi- b -value MRI can be denoised model-free with our PCA-denoising strategy that reduces noise to a level similar to synthetic MRI, but without introducing systematic errors associated with the synthetic MRI method.

Objectives To determine the ability of multi-parametric, endogenous contrast MRI to detect and quantify fibrosis in a chemically-induced rat model of mammary carcinoma. Methods Female Sprague-Dawley rats (n=18) were administered with N -methyl- N -nitrosourea; resulting mammary carcinomas underwent nine-b-value diffusion-weighted (DWI), ultrashort-echo (UTE) and magnetisation transfer (MT) magnetic resonance imaging (MRI) on a clinical 1.5T platform, and associated quantitative MR parameters were calculated. Excised tumours were histologically assessed for degree of necrosis, collagen, hypoxia and microvessel density. Significance level adjusted for multiple comparisons was p=0.0125. Results Significant correlations were found between MT parameters and degree of picrosirius red staining (r > 0.85, p < 0.0002 for k a and δ, r < -0.75, p < 0.001 for T 1 and T 1s , Pearson), indicating that MT is sensitive to collagen content in mammary carcinoma. Picrosirius red also correlated with the DWI parameter fD* (r=0.801, p=0.0004) and conventional gradient-echo T 2 * (r=-0.660, p=0.0055). Percentage necrosis correlated moderately with ultrashort/conventional-echo signal ratio (r=0.620, p=0.0105). Pimonidazole adduct (hypoxia) and CD31 (microvessel density) staining did not correlate with any MR parameter assessed. Conclusions Magnetisation transfer MRI successfully detects collagen content in mammary carcinoma, supporting inclusion of MT imaging to identify fibrosis, a prognostic marker, in clinical breast MRI examinations. Key Points • Magnetisation transfer imaging is sensitive to collagen content in mammary carcinoma. • Magnetisation transfer imaging to detect fibrosis in mammary carcinoma fibrosis is feasible. • IVIM diffusion does not correlate with microvessel density in preclinical mammary carcinoma.

BACKGROUND AND PURPOSE:The superior soft-tissue contrast of 4D-T2w MRI motivates its use for delineation in radiotherapy treatment planning. We address current limitations of slice-selective implementations, including thick slices and artefacts originating from data incompleteness and variable breathing. MATERIALS AND METHODS:A method was developed to calculate midposition and 4D-T2w images of the whole thorax from continuously acquired axial and sagittal 2D-T2w MRI (1.5 × 1.5 × 5.0 mm3). The method employed image-derived respiratory surrogates, deformable image registration and super-resolution reconstruction. Volunteer imaging and a respiratory motion phantom were used for validation. The minimum number of dynamic acquisitions needed to calculate a representative midposition image was investigated by retrospectively subsampling the data (10-30 dynamic acquisitions). RESULTS:Super-resolution 4D-T2w MRI (1.0 × 1.0 × 1.0 mm3, 8 respiratory phases) did not suffer from data incompleteness and exhibited reduced stitching artefacts compared to sorted multi-slice MRI. Experiments using a respiratory motion phantom and colour-intensity projection images demonstrated a minor underestimation of the motion range. Midposition diaphragm differences in retrospectively subsampled acquisitions were <1.1 mm compared to the full dataset. 10 dynamic acquisitions were found sufficient to generate midposition MRI. CONCLUSIONS:A motion-modelling and super-resolution method was developed to calculate high quality 4D/midposition T2w MRI from orthogonal 2D-T2w MRI.

ObjectiveRegorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection.DesignPatients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (Ktrans), enhancing fraction (EF) and their product KEF (summarised median values of Ktrans× EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal RAS mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies.ResultsTwenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07–1.04), p=0.06).ConclusionsCombining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications.

ConclusionOn an anthropomorphic phantom the error in dose calculated on CBCT is within 1%; this error is 2% larger going from phantom to patient images.Thus dose calculations on CBCT are feasible within ~3% accuracy when transferring structures rigidly between similar images.

The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits.